There is a high need for biomaterials that can be used in biomedical applications, including those related to treatment and management of disease as well as in the fabrication of new-generation medical devices and implants. Currently, there are a limited number of biomaterials that have properties that will allow them to perform in a reproducible, accurate, selective, and sensitive manner, and that are amenable to integration into devices that can be employed in a variety of applications (e.g., biosensors, delivery systems, diagnostic and high throughput screening platforms, etc.), those being in vitro or in vivo. Given the complex and multidisciplinary nature of the problem, a successful approach should integrate knowledge from a number of scientific and engineering disciplines. To that end, the overall goal of this project is to design biologically inspired, advanced biomaterials that integrate protein recognition within micro- and nano-fabricated structures. The smart biomaterials are based on the recognition of proteins for specific ligands and their subsequent response to them. These proteins undergo conformational changes upon binding specific ligands and will be employed to engineer biomaterials with tailored response characteristics. Moreover, by rationally designing the proteins and employing genetic engineering techniques (e.g., gene fusion, site-directed mutagenesis, etc.) we will be able to fine-tune their dynamic response. These biologically inspired materials will be built into novel nanofabricated structures as to synergistically enable new devices/material with unprecedented properties.